(1) Field of the Invention
The present invention relates generally to harvesting of synovial villi from a joint and introducing explants or separated cells from the synovium into damaged tissues to repair the injured tissues. Specifically, the present invention relates to repairing tissues or organs such as a joint or elsewhere. The present invention also relates to harvesting omentum from the abdomen and introducing explants or separated cells from the omentum into damaged tissues to repair the injured tissues or organs in the abdomen or elsewhere.
(2) Description of the Related Art
Hematopoietic stem cells (HSCs) are cells which are capable of dividing and differentiating into any cell type of the blood. Two types of HSCs are known to exist: long-term and short-term HSCs. Long-term HSCs cell cycle and divide each day, while short-term HSCs differentiate into lymphoid and myeloid precursors. The lymphoid precursors give rise to T cells, B cells and natural killer cells. The myeloid precursors give rise to monocytes, macrophages, neutrophils, eosinophils, basophils, megakaryocytes, and erythrocytes. Hematopoietic stem and progenitor cells harvested for transplantation have typically come from bone marrow. Recently however, peripheral blood and umbilical cord blood have been used as a source for these cells. Peripheral blood stem cells (PBSC) have been mobilized by various techniques, since stem and progenitor cells are a very low percentage of the cells found in peripheral blood. An apheresis device is used to collect from a patient and automatically separate specific cells from whole blood. Afterwards the remaining blood components are returned to the patient, typically using a dual lumen catheter. Plasma, red blood cells, platelets, and white blood cells can be specifically removed by centrifugation in continuous mode while the remaining blood components are returned to the patient. Blood components which can be separated include plasma (plasmapheresis), platelets (plateletpheresis), and leukocytes (leukapheresis). Apheresis can be used to separate mononuclear cells (MNC) which include stem cells.
The stem and progenitor cells in peripheral blood can be increased prior to apheresis by myelosuppressive chemotherapy mobilization techniques and other drugs. Various myelosuppressive regimens are available including cyclophosphamide. Unfortunately, using such chemotherapy to mobilize PBSC can have an associated risk of toxicity. Since not every patient who must receive stem and progenitor cells will require chemotherapy for an associated illness, this is not always an appropriate option for mobilizing stem and progenitor cells from bone marrow. Recent approaches to mobilizing stem and progenitor cells utilize hematopoietic growth factors. Such growth factor mobilization procedures use filgrastim (granulocyte colony-stimulating factor [G-CSF]), sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]), or combinations thereof. G-CSF is administered subcutaneously at a dose of 10 to 16 micrograms per day (μg/d), which typically results in a peak level of circulating progenitor cells at day 4 to 7 after starting G-CSF administration. Other growth factors such as stem cell factor (SCF) can also be used to mobilize stem cells into the peripheral blood. Stress, injury, estrogen therapy, physical training, and nanopulses have all been shown to mobilize cells progenitor and stem cells in the peripheral blood.
Alternatively, stem cells can be isolated from adult human synovial membrane as described by De Bari et al. Arthritis Rheum. 2001 August; 44(8):1928-42. Cultured fibroblast-like cells derived from adult human synovial membrane have been characterized by Vandenabeele et al. Arch Histol Cytol. 2003 May; 66(2):145-53. Skeletal muscle repair by stem cells from synovial membrane was described by De Bari et al. Journal of Cell Biology 160:6 909-918 (2003). However, De Bari et al. Arthritis & Rheumatism vol 50 no. 1, pp. 142-150 found that in-vitro differentiated stem cells from synovial membrane failed to form ectopic cartilage. Kowalczyk et al. suggests that the omentum major may be another a potential source of osteogenic cells for tissue engineering.
U.S. Pat. No. 6,080,194 to Pachence et al. disclose a porous collagen-based implant for use in the repair of cartilage lesions. U.S. Pat. No. 6,602,294 B1 and U.S. Patent Application Publication No. 2004/0028717 A1 to Sittinger et al. disclose implantable substrates for the healing and protection of connective tissue, preferably cartilage. U.S. Pat. No. 5,842,477 to Naughton et al. teaches methods for repairing cartilage by implanting biocompatible scaffold in combination with periosteal and/or perichodrial tissue to provide a source of chondrocyte progenitor cells, chondrocytes and other stromal cells for attachment to the scaffold.
While the related art teach chemical or hematopoietic growth factor mobilization of stem cells from bone marrow and various implantable substrates for the healing of cartilage, there still exists a need for methods of harvesting stem and progenitor cells from the body which can be introduced into tissues of a patient to repair and regenerate damaged tissue.